Drug repurposing: a systematic review on root causes, barriers and facilitators

Repurposing is a drug development strategy receiving heightened attention after the Food and Drug Administration granted emergency use authorization of several repurposed drugs to treat Covid-19. There remain knowledge gaps on the root causes, facilitators and barriers for repurposing. METHOD: This systematic review used controlled vocabulary and free text terms to search ABI/Informa, Academic Search Premier, Business Source Complete, Cochrane Library, EconLit, Google Scholar, Ovid Embase, Ovid Medline, Pubmed, Scopus, and Web of Science Core Collection databases for the characteristics, reasons and example of companies deprioritizing development of promising drugs and barriers, facilitators and examples of successful re-purposing.

We identified 11,814 articles, screened 5,976 for relevance, found 437 eligible for full text review, 115 of which were included in full analysis. Most articles (66%, 76/115) discussed why promising drugs are abandoned, with lack of efficacy or superiority to other therapies (n = 59), strategic business reasons (n = 35), safety problems (n = 28), research design decisions (n = 12), the complex nature of a studied disease or drug (n = 7) and regulatory bodies requiring more information (n = 2) among top reasons. Key barriers to repurposing include inadequate resources (n = 42), trial data access and transparency around abandoned compounds (n = 20) and expertise (n = 11). Additional barriers include uncertainty about the value of repurposing (n = 13), liability risks (n = 5) and intellectual property (IP) challenges (n = 26). Facilitators include the ability to form multi-partner collaborations (n = 38), access to compound databases and database screening tools (n = 32), regulatory modifications (n = 5) and tax incentives (n = 2).